Models and methods of using same for testing medical devices

ABSTRACT

Disclosed herein are synthetic anatomical models that are designed to enable simulated use testing by medical device companies, medical device designers, individual inventors, or any other entity interested in the performance of medical devices. These models are unique in possessing a level of complexity that allows them to be substituted for either a live animal, an animal cadaver, or a human cadaver in the testing of these devices. These models are further characterized by a similarity of geometry, individual component physical properties, and component-to-component interfacial properties with the appropriate target tissue and anatomy.

BACKGROUND OF THE INVENTION

During the development of any new medical device, various tests may berequired, including the characterization of physical properties(geometric, mechanical, electrical, electromagnetic, thermal, chemical,etc), the evaluation of overall device performance (numerical simulationor simulated use testing), or testing to determine the effect of thedevice on living tissues. These development tests may be broadlyclassified as either biological tests, theoretical tests, or physicaltests, although there are areas where these testing classes overlap oneanother.

Biological testing generally involves an analysis of the interactionbetween the device and human or animal tissues. The biological teststhat are performed first are generally biocompatibility tests, whichevaluate the tendency of the device to cause damage to living tissues bymere presence of the materials comprising the device. Later on in thedevelopment cycle, the device may be tested in a live animal (animalstudy) or a human patient (clinical trial) to determine the ability ofthe device to perform its intended use and to evaluate safety andefficacy (device performance). Animal studies represent a special typeof test known as simulated use testing, so called because the animal isa simulation of the actual use (human) environment.

Theoretical or computational tests may include finite element analysis,kinematic analysis, and computational fluid dynamics. These tests employknowledge of the physical properties (strength, mass, density,viscosity, etc) of the device and actual use environment to construct acomputer model of the device—tissue system. This type of model may thenbe used to predict device performance, the tendency of the device tofail, and possibly the tendency of the device to cause injury. Ofcourse, these models are limited by the assumptions made in theirderivation and the computational power of the computer. Unfortunately,it may be difficult to quantitatively describe a device, and moreimportantly the actual use environment, in sufficient detail to yieldrealistic results.

Physical testing essentially evaluates the design of the device. Thatis, this physical testing may involve; (1) the measurement of devicegeometry such as lengths, diameters, and wall thicknesses, (2) themeasurement of mechanical properties such as tensile strength andstiffness, (3) the measurement of other device characteristics such ascolor, thermal conductivity, dielectric properties or other properties,or (4) simulation testing involving trial use of the device in somemodel of the actual use environment. The purpose of this simulationtesting is to evaluate the safety (tendency to injure) and efficacy(performance characteristics) of the device, and in general to evaluatethe ability of the device to perform it's intended use. As previouslystated, animal studies are one important form of simulation test. Othervehicles (the simulated environment) for this type of testing includecadavers (both human and animal) and benchtop fixtures, which areman-made representations of a particular target anatomy.

The new FDA quality system regulation (QSR) now requires testing undersimulated or actual use conditions for all nonexempt Class II and ClassIII medical devices. Not all manufacturers perform actual use (humanclinical trial) testing for every medical device, so in these casessimulation testing is definitely a requirement. At least fourtraditional simulation options are available to meet this requirement,each with its own advantages and drawbacks. These four generalapproaches (Table I) to simulation testing involve theoretical(computer) models, benchtop (physical) models, cadaver (human or animal)models, and live animal models. Once again, human subjects are alsoemployed in the development of many medical devices, but since humansrepresent the actual use environment, these tests (clinical studies) arenot considered simulation tests.

TABLE I The four general approaches to simulation testing including theenvironment and models involved. Theoretical Model Benchtop ModelCadaver Model Live Animal In vitro In vitro In vitro In vivo Theoreticalor Physical Human or Animal study computational properties animal modelmodel cadaver

Typical medical device development schemes generally involve testingearly prototypes in simple bench top test fixtures. Feedback from thesetests shape the product through design revisions that are subsequentlyevaluated using the same model. However, since this process isiterative, as the design matures the models that are needed generallybecome more complex. For example, a new coronary catheter may undergoinitial testing in simple plastic tubes, followed by glass modelsdesigned to mimic the size and geometry of the coronary vasculature. Theproduct may experience a series of changes resulting from these testsuntil the designer is satisfied with performance, and once a certainlevel of confidence is achieved the testing will proceed to the nextavailable model. In the medical device industry this model is generallya live animal.

In practice, the medical device industry typically employs one or moreof the four previously mentioned (Table I) model types in simulationtesting prior to seeking approval for human use (a clinical trial). Ofcourse, common sense dictates that the model selected be representativeof actual use conditions, but only the clinical trial, which is not asimulation test, fully satisfies this criteria. Unfortunately, humansubjects are unavailable for use until late in the development cycle dueto risk, regulatory, and ethical considerations. A live animal model hastherefore traditionally been the next best choice.

Animal models are currently the gold standard of pre-clinical trialmedical device simulated use testing. In fact, the quality of dataproduced in these studies can be very high, particularly if the properanimal model is selected, the device and protocol are well designed, andthe correct number of animals is used. Designed experiments are possibleand are commonly employed, but require an increase in the number ofanimals. These tests are also performed under physiological (for theanimal) conditions. Unfortunately, these studies are expensive becauseof the staff and facilities required to support the work. A registeredfacility must be contracted to run the study and care for any animalspurchased, a surgeon must be retained to perform the required proceduresand to generate the study protocol, and the services of a veterinarian,anesthesiologist, and surgical aide are also required. These studies caneasily exceed $100,000 in total costs, and grow even more costly as thenumber of animals is increased.

The inability to test prototype devices on human subjects is the reasonmedical device developers resort to animal studies in the first place.Still, animal models suffer from a whole range of unique problems,including the many deviations between human and animal anatomy andphysiology, the confounding effects of variation between individualanimals, and the unpredictability that arises from using a model that isextraordinarily complex.

Animal models may include live canine, porcine, or bovine specimens,among others. While these animals do offer an in vivo environment, theiranatomy and physiology differs significantly from that of a human. Thegreat expense and specialized facilities required limit their in-houseuse. Reproducibility may also be an issue as both inter- andintrasubject variability are difficult to control. Additionalconsiderations include contention with the Animal Welfare Act, thesignificant expense associated with contracting regulated facilities andmedical practitioners, and the risks related to handling biohazardousmaterials.

To get around these issues, developers tend to gravitate toward simplerand more accessible models such as cadavers and benchtop fixtures.Unfortunately, there tends to be an inverse relationship between theusefulness and complexity of the model employed. For example, cadavertissues provide an accurate representation of anatomical geometry, butthe required chemical preservation greatly alters the physicalproperties of the tissues. In addition, biological temperatures andflows cannot generally be simulated, subjects are difficult to sourceand maintain in useful quantities, and an educational institution mustalmost always be contracted (at considerable expense) to perform thestudy.

These factors drive early stage medical device developers to simplebenchtop fixtures made (usually) in house by the developer.Unfortunately, these models are typically designed by individualslacking an understanding of anatomy and physiology, and are usuallyfabricated from typical engineering materials such as metal, glass, andplastic. While an argument may be made that these models are better thannothing, they are certainly not representative of actual use conditions.Furthermore, engineers in general will agree that the quality of testdata is dependent on the good logic behind the test protocol and thequality of the model employed. A poor model is therefore more likely toyield misleading data, and a design based at an early stage upon thisdata is more likely to require correction at a later stage indevelopment.

BRIEF SUMMARY OF THE INVENTION

The use of a poorly conceived model in development testing will lead toreduced product quality, increased development costs, and greatlylengthened product timelines. Fortunately, these failures may be avoidedby employing an intelligent development scheme in conjunction with ahigh quality model. Accordingly, the subject invention pertains tocomplex synthetic anatomical models that are designed to enablesimulated use testing by medical device companies, medical devicedesigners, individual inventors, or any other entity interested in theperformance of medical devices. These models are unique in possessing alevel of complexity that allows them to be substituted for either a liveanimal, an animal cadaver, or a human cadaver in the testing of thesedevices. These models are further characterized by a similarity ofgeometry, individual component physical properties, andcomponent-to-component interfacial properties with the appropriatetarget tissue and anatomy.

The model embodiments of the subject invention may serve as a highlysophisticated bench top model that is designed to be used by medicaldevice developers both early and late in the development process. Thesemodels mimic not only the geometry of the target anatomy, but also thephysical properties of the living tissues that contact the device.

One important feature of certain embodiments of the subject invention isthe implementation of synthetic analog materials that can simulate thephysical properties of living tissues. These analogs are in most caseshydrogel materials that are designed on the basis of physical testsperformed on actual target tissues. For example, a particular analogmaterial might be designed to exhibit a tensile strength close to 10 kPato mimic a target tissue that exhibits a tensile strength of 10 kPa. Oneor more components made from these analog materials are then assembledinto a configuration that mimics both the size and geometry of thetarget organ. The resulting bench top model may therefore be describedas a synthetic organ, and it will respond to certain physical stimulus(the device) in a fashion that is similar in many respects to the actualorgan.

Model embodiments of the subject invention may be nearly as simple touse as a bench top fixture, but provide feedback that is superior inmany respects to cadaver tests, animal studies, and even human clinicaltrials. In fact, a prototype device may be tested not just in terms ofdevice performance, but also in terms of effect on the target anatomy.This is possible because the device interfacing portion of the model isremovable, allowing a quasi-histological examination of the targetanatomy after each use. In addition, because the models are artificialand mass produced, multiple tests may be performed either underidentical conditions or by altering only the test parameters(temperature, flow, contact angle, etc) desired. This capability helpsto eliminate the statistically confounding effect of model variationthat plagues cadaver, animal, and human subject studies, and alsoenables the use of designed experiments to explore device-tissueinteractions and interactions between various design parameters.

Some embodiments of the subject invention have several advantages overtypical bench top fixtures. Some fixtures in use today may be designedto mimic the overall size and geometry of a particular target tissue,and the best of these are also designed to work at body temperature inthe presence of fluids. However, the use of engineering materials in theconstruction of these models make them dissimilar to the target anatomyin a profound way. This calls into question the value of any datacollected, even when designed experiments are employed. In addition,these models may only be used to predict device performance, not theeffect of the device on the target tissue.

In contrast, some embodiments of the subject invention enable apotentially large number of tests to be completed in an environment thatis both geometrically and mechanically similar to the target anatomy.These tests may be performed by an engineering technician on a labbench, but the tests still produce very high quality data. Also, becausethis data may be generated early in the development cycle, design errorsare discovered sooner, leading to a shorter cycle and a reduceddevelopment budget. Further, unlike traditional bench top testing, useof embodiments of the subject invention allows the user to predict how adevice will actually function in the human body, and since the effect ofthe device on the target tissue can be predicted by way of thequasi-histological examination, the risk to the patient may be predictedfrom the beginning of the process.

Use of embodiments of the subject invention also have several advantagesover cadaver studies. Cadaver models provide a fairly accuraterepresentation of size and geometry, but the mechanical properties ofthe target anatomy are altered by death of the subject and by therequired tissue preservation techniques. It is impossible to use thesemodels at normal body temperature or in the presence of fluids, and theycannot be employed to accurately predict the physical effect of thedevice on the target tissue. An educational institution must almostalways be contracted (along with a principal investigator) to performthe study, and since the specimens are difficult to source it is commonto run only a single test. Biohazards are an additional risk.

In contrast, use of embodiments of the subject invention enables thegeneration of animal study quality data (in a much greater quantity)using a simple bench top setup that may be used by an engineeringtechnician. The need to contract with research facilities, employ costlymedical practitioners, and also any exposure to biohazards iseliminated. In addition, these models may be used at body temperature inthe presence of any real or simulated physiologic fluid, and since thedevice contacting portions of the model may be removed and replaced, anunlimited number of tests may be performed.

Models according to embodiments of the subject invention have severaladvantages over live animal models. As previously stated, the quality ofdata produced in these studies can be very high, particularly if theproper animal model is selected, the device and protocol are welldesigned, and the correct number (more is always better) of animals isemployed. However, a registered facility must be contracted to run thestudy and care for any animals purchased. A surgeon must be retained toperform the required procedures, generate the study protocol, and toensure approval from the animal care and use committee of the facility.The services of a veterinarian, anesthesiologist, and surgical aide arealso required. Needless to say, these studies are very expensive andgrow ever more costly as the number of animals is increased. The cost ofdiscovering a design flaw at this stage is very high, possibly causingmodification, termination, or repetition of the study. Biohazards arealso a significant risk.

In effect, the inclusion of models according to the subject invention inthe development process allows the collection of animal study qualityperformance data (Table II) at a risk level that is normally associatedwith bench top studies. In fact, by employing this technology early onin the development process, vital feedback on device performance may becollected before erroneous assumptions can adversely affect the design.This capability not only reduces the probability of costly late stagedesign changes, but also shortens the project timeline and reduces theoverall cost of development. In addition, these models may be used in anordinary laboratory by engineering personnel. The need to own orcontract with research facilities, pay for costly medical practitioners,and absorb risks associated with biohazard exposure are all eliminated.An innocent life (the animal) is also spared.

TABLE II A comparison of the various model types available in industry.Model Criteria Positive Attributes Negative Attributes Lab PredictTarget Tissue Medical Biohazard Live Quality Attributes Testing TissueAnatomy Properties Contractors Exposure Animal Data Relative ModelPossible Damage Modeled Modeled Required Risks Loss Quality Expense ARMX X X X High Med Fixture X X Low Low Cadaver X X Med Med Animal X X X XX High High Human X X X X X High Extreme

These and other advantageous aspects of the subject invention aredescribed in the detailed description below, description of thedrawings, and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a perspective view of one embodiment of the subjectinvention directed to a femoral artery model.

FIG. 2 shows a perspective view of one embodiment of the subjectinvention directed to a luminal structure simulating a femoral artery.

FIG. 3 shows a perspective view of one embodiment of the subjectinvention directed to a luminal structure model simulating vasculature.

FIG. 4 shows a frontal view of one embodiment of the subject inventiondirected to a torso model.

FIG. 5 shows a perspective view of one embodiment of the subjectinvention directed to a heart model.

FIG. 6 shows a perspective view of one embodiment of the subjectinvention directed to a neurovasculature model.

FIGS. 7A-B are photographs showing fixtures for bench top testing inaccord with the teachings herein.

FIG. 8 is a rendering of a bottom view of a brain showing the level ofdetail of neurovasculature that may be implemented into aneurovasculature model.

FIG. 9 are photographs representing the impact of each device on thetissue analog is illustrated in FIGS. 9A-C

FIG. 10 is a cross-sectional view of a brain showing internalvasculature of the brain that may be simulated in a model embodiment ofthe subject invention.

DEFINITIONS

It is important to an understanding of the present invention to notethat all technical and scientific terms used herein, unless definedherein, are intended to have the same meaning as commonly understood byone of ordinary skill in the art. The techniques employed herein arealso those that are known to one of ordinary skill in the art, unlessstated otherwise. For purposes of more clearly facilitating anunderstanding of the invention as disclosed and claimed herein, thefollowing definitions are provided.

The term “analog material” as used herein refers to a material orcombination of materials designed to mimic one or more physicalproperties of a relevant target tissue. Analog materials may include,but are not limited to, hydrogel, silicone rubber, natural rubber, otherthermosetting elastomers, other thermoplastic elastomers, acrylicpolymers, other plastics, ceramics, cements, wood, styrofoam, metals,actual human tissues, actual animal tissues, and any combinationthereof. Each component part in model embodiments may be constructedfrom one or more analog materials.

The term “hydrogel(s)” as used herein refers to a unique class ofmaterials that contain a large amount of water and generally exhibit ahigh degree of elasticity and lubricity. These materials are ideal forsimulating the physical properties of many living soft tissues.Hydrogels are materials that are wetable and swell in the presence ofmoisture and retain water without dissolving. These materials aregenerally constructed of one or more hydrophilic polymer molecules,although copolymerization with hydrophobic monomers may also lead to theformation of a hydrogel. These materials are generally elastic, andexhibit a three-dimensional network that is either crosslinked directlyby chemical bonds or indirectly through cohesive forces such as ionic orhydrogen bonding.

The term “luminal structure” refers to any structure in the body throughwhich a substance flows through, including, but not limited to, thearterial and venous vasculature anywhere in the anatomy, the trachea,the sinuses, the oral cavity, the esophagus, the urinary tract, the earcanal, certain portions of the male and female reproductive system, thebile ducts, other portions of the digestive system, and any other partof the anatomy that resembles a luminal structure or cavity. Dependingon the context in which the term luminal structure is used herein, itmay refer to a representative anatomical structure in a living ordeceased animal (i.e., native structure), or may refer to an artificialluminal structure intended to model such native structure. As describedherein, artificial luminal structure may actually pertain to a luminalstructure removed from a living or deceased animal but which is used asa model.

Accordingly, the term “geometrically mimic” as used herein refers toconfigurations of models that comprise a similar geometric feature ofthe target anatomical structure to be mimicked, such as length, width,diameter, thickness, cross-section, and/or, in most cases general shapeof a particular target anatomy.

The term “lumen possessing human or nonhuman anatomical structure” asused herein refers to any anatomical structure that comprises as one ofits features a lumen. In its most basic sense it is directed to theactual luminal structure itself such as a vessel, duct, tract, passage,orifice, airway, etc., as found in an a human or nonhuman animal. It mayalso be directed to a section of the anatomy that comprises a luminalstructure cooperative with other tissue(s). For example, in no wayintended to be limiting, it may pertain to a structure generally shapedlike an organ, such as a heart, having luminal structures cooperative tothe exterior and/or interior of the structure, such as in a heartexample, the coronary arteries and aorta. In another example, notintended to be limiting, but merely for illustrative purposes, it may bea limb or a portion thereof, that contains within it one or more majorblood vessels. In another example it may be a torso of a human body thathas major blood vessels, ducts, and/or tracts comprised within.

In certain model embodiments, one or more components may be cooperativewith other one or more components. The term cooperative in this contextmeans that such cooperative components are contiguous, engaged, orintegrated with one another. Further, components cooperative with oneanother may be designed to be dissociable, i.e., removably cooperative.

DETAILED DESCRIPTION

The interaction of a foreign body with living tissues results incomplications that are related to, among other things, shear forces,normal forces, abrasive action, blunt trauma, pressure necrosis, orother physical insults caused by the invading device. Not only arestudies to predict the long-term effect of this invasion difficult andexpensive to conduct, but when live patients are involved the studiesoften yield inconclusive results. As an alternative to using thesepatients, a bench top model may be employed to physically simulate theinsult to the tissue as a relatively inexpensive, easily repeatable, andlogical first step before resorting to animal studies and clinicaltrials. However, for this approach to be productive, the model employedmust be representative of the actual target anatomy in which the medicaldevice will normally be used.

The subject invention pertains to complex synthetic anatomical modelsthat are designed to enable simulated use testing by medical devicecompanies, medical device designers, individual inventors, or any otherentity interested in the performance of medical devices. These modelsare unique in possessing a level of complexity that allows them to besubstituted for either a live animal, an animal cadaver, or a humancadaver in the testing of these devices. These models are furthercharacterized by a similarity of geometry, individual component physicalproperties, and component-to-component interfacial properties with theappropriate target tissue and anatomy.

The model embodiments of the subject invention create a test environmentsimilar in many ways (mechanical properties, physical properties,temperature, flow rate, viscosity, etc) to that of a living animal. Inaddition, individual tests may be repeated as many times as desiredunder identical or (if desired) altered conditions. Also, thetissue-contacting portion of the model may be removed to allow aquasi-histological examination to be performed after each test, animportant feature that allows the engineer to predict the tendency of aparticular device to inflict injury (or other effect) on the patient.

A study employing the models of the subject invention allows thegeneration of data that is comparable, and in some ways superior to thatof an animal study. Furthermore, since these studies employ areproducible model, the statistically confounding effect of variationbetween animals is eliminated. The ability to perform truly reproducibletests allows interactions between the device and the model, as well asinteractions between multiple design parameters to be evaluated, a taskwhich is nearly impossible with an animal study. In addition, theexpense related to the purchase and housing of animals, contractingregistered facilities, and retaining medical practitioners iseliminated. The risks associated with biohazards are also eliminated anda number of innocent animals are spared.

In one embodiment, the subject invention pertains to artificialanatomical models that geometrically mimic an anatomical structurecomprising a luminal structure.

In another embodiment, the subject invention contains a luminalstructure with segments or portions thereof that are constructed fromhydrogel material. Alternatively, the entire luminal structure may beconstructed from hydrogel material.

In yet another embodiment, the subject invention is directed to aluminal structure with segments or portions thereof that are constructedfrom standard engineering materials, but that are coated on the interior(medical device contacting) portion of the luminal structure with ahydrogel or hydrophilic material.

In a specific embodiment, the subject invention contains a luminalstructure structure with segments or portions thereof that areconstructed from either standard engineering materials or hydrogelmaterials, but with supporting (non-device contacting) structuresconstructed from hydrogel materials.

Available benchtop fixtures are designed to mimic the general size andgeometry of a target tissue, and the best of these are also designed towork at body temperature in the presence of fluids. However, the typicaluse of engineering materials in their construction makes these commonmodels dissimilar to the target anatomy and calls into question thevalue of any data collected using them, even when designed experimentsare employed. In addition, these models may only be used to predictdevice performance, not the effect of the device on the target tissue.

In comparison, the model embodiments of the subject invention enable forthe first time a potentially large number of tests to be completed andrepeated under identical conditions in an environment that is bothgeometrically, mechanically, and physically similar to the targetanatomy. An engineering technician may perform these tests on a simplebenchtop setup, while still generating very high quality of data. Also,because this data is provided early in the development process, designerrors may be discovered earlier; leading to a shorter development cycleand a reduced development budget. Finally, since the effect of thedevice on the target tissue can be predicted, device quality isimproved.

Available cadaver models can provide a fair representation of anatomicalgeometry, but the mechanical and physical properties of the targetanatomy are altered by preservation techniques. It is impossible to usethese models at normal body temperature or in the presence of testfluids, and they cannot be employed to accurately predict the physicaleffect of the device on the target issue. An educational institutionmust generally be contracted, along with a principal investigator, toperform the study, and since the specimens are difficult to source it iscommon to run only a single test. Biohazards are an additional risk.

In comparison, the model embodiments of the subject invention facilitatethe generation of animal study quality data using a simple benchtopsetup that can be used by an engineering technician. These models may beused at body temperature in the presence of any real or simulatedphysiologic fluid, and since the device contacting portions of the modelmay be removed and replaced, an unlimited number of tests may beperformed. The need to contract with research facilities, employ costlymedical practitioners, and expose staff to the risks associated withbiohazards are eliminated.

The models of the subject invention are characterized by a similarity ofgeometry, of individual component physical properties, and ofcomponent-to-component interfacial properties with living tissue. On thesimplest level, individual model components are fabricated such thatthey mimic the geometry of a particular target anatomy.

The geometric data needed for fabrication is typically obtained in twoways. The traditional approach is to obtain data from the literature onmorphology or from cadaver measurements. While not a bad approximation,this method is time-consuming and permits a large degree of error. Abetter method would be to get the geometric data directly from a patientor from sources such as the Visible Human Project.²

After collecting the appropriate geometric data, the individual modelcomponents may be fabricated from appropriate analog materials.Depending on the complexity of the part and the type of materials used,the individual component might be molded, extruded, or machined. Forcomplex geometries, however, these techniques may become cumbersome andexpensive. In these cases rapid prototyping techniques such asstereolithography offer a relatively inexpensive alternative. Techniquesare being developed that allow actual patient data (obtained from MRI orspiral-CT images) to be fed directly into the rapid prototyping system,thus replicating the patient's anatomy exactly. This technology allowsfor the production of extremely realistic simulations.

The models of the subject invention are constructed from multiplecomponents, and these individual components are fabricated in such a waythat they mimic the geometry (length, width, diameter, thickness,cross-section, shape, etc) of a particular portion of the target anatomythat is relevant to the medical device under test.

The analog materials used to manufacture the individual components ofthe subject invention are formulated to exhibit one or more physicalcharacteristics of a target living tissue such as, but not limited to,uni-axial or multi-axial tensile strength or modulus, uni-axial ormulti-axial compressive strength or modulus, shear strength or modulus,coefficient of static or dynamic friction; surface tension; wettability;water content; electrical resistance and conductivity; dielectricproperties; optical absorption or transmission, thermal conductivity,porosity, moisture vapor transmission rate, chemical absorption oradsorption; or combinations thereof. Each analog material is designed sothat the physical properties of the analog will match the physicalproperties of the relevant tissue on which the analog is based. Morespecifically, each analog material is formulated so that the physicalproperty or properties of the analog fall within a range that 50% ormore similar to the targeted physical property or properties of therelevant living tissue on which the analog material is based.

The aforementioned listed physical characteristics are well understood,and may be determined by well-established techniques. Referencesteaching the determination of different physical properties (in no wayintended to be an exhaustive list) include the following:

(1) Shigley, J. E., and Mischke, C. R. Mechanical Engineering Design,5^(th) Ed., McGraw-Hill, 1989.

(2) Harper, C. A., Handbook of Materials for Product Design, 3^(rd) Ed.,McGraw-Hill, 2001.

(3) Askeland, D. R., The Science and Engineering of Materials, 2^(nd)Ed., PWS-Kent, 1989.

(4) LaPorte, R. J., Hydrophilic Polymer Coatings for Medical Devices,Technomic Publishing, 1997

(5) Hayt, W. H., and Kemmerly, J. E., Engineering Circuit Analysis,4^(th) Ed., McGraw-Hill, 1986.

(6) Park, J. B., and Lakes, R. S., Biomaterials, An Introduction, 2^(nd)Ed., Plenum Press, 1992.

(7) Lindenburg, M. R., Editor, Engineer in Training Manual, 8^(th) Ed.,Professional Publications, 1992.

Particular teachings of certain physical properties are noted(references numbers related to preceding list):

Tensile strength and modulus, both measured in Pascal (Pa)—Ref 1, pg186.

Compressive strength and modulus, both measured in Pascal (Pa)—Ref 2, pg718.

Shear strength and modulus, both measured in Pascal (Pa)—ASTM StandardD3165-00, Standard Test Method for Strength Properties of Adhesives inShear by Tension Loading of Single-Lap-Joint Laminated Assemblies.

Coefficient of static and dynamic friction, a dimensionless number—Ref7, pg 445.

Surface tension, measured in dynes/cm—Ref 6, pg 57.

Wettability, measured in terms of contact angle (degrees)—Ref 4, pg 3.

Water content, measured in mass percent (%)—Ref 4, pg 41.

Electrical resistance and conductance, measure in ohm for resistance andmho for conductance—Ref 5, pg 25.

Dielectric properties, measured in various units—ASTM Standard E2039-04Standard Test Method for Determining and Reporting Dynamic DielectricProperties.

Optical absorption and transmission, measured in cm⁻¹—Ref 3, pg 739.

Thermal conductivity, measured in cal/(cm-s-C)—ASTM Standard D5930-01Standard Test Method for Thermal Conductivity of Plastics by Means of aTransient Line-Source Technique.

Porosity, measured in percent (%)—Ref 3, pg 490.

Moisture vapor transmission rate, measured in g/(mil-in²)—Ref 2, pg 941.

The individual components of the subject invention are assembled in sucha way that the interaction between adjacent components yields theoverall interaction expected in the actual target tissue. That is, theinterfacial properties (bond strength, component-to-component friction,etc) between the various model components are designed to simulate theinteraction between the relevant tissues in the target anatomy.

In designing particular embodiments of the subject invention, therelevant anatomy may be conceptually divided into discrete sections thatwill form the individual components of the model. For example, a modelof the femoral artery might employ at least two (and possibly many more)analog materials: one for the femoral artery component and one for thesupporting tissue component. Furthermore, these analog materials areformulated to mimic one or more properties of the target tissue. Thisgenerally involves implementation of two design parameters (modeledproperties and data source) to be determined.

The first design parameter typically entails selecting physicalproperties that are important for the analog material to mimic in thedecided application. These properties will vary depending on the type ofdevice under test, the target anatomy, and the general objective of thetesting. For example, if one objective is to determine the tissue damagecaused by a device tracking through the femoral artery it would beadvantageous to include abrasion resistance in the properties list. Inaddition, if a further objective is to simulate the tendency of thedevice to penetrate the artery wall then penetration resistance or shearstrength might be included in the list as well. Any number of propertiesmay be included in the target properties list, but it should be notedthat as this list gets longer it becomes progressively more difficult tosatisfy all of the design requirements. In fact, in typical embodiments,if a particular component requires an analog material with more thanthree target properties it might be better to separate the componentsinto multiple parts.

The second design parameter typically involves selecting the source ofthe physical properties data. That is, it should be determined if themodel will be based on human or animal (or both) tissue properties. Oncethis is determined, the data may either be drawn from the literature orgenerated directly by performing the appropriate physical tests onactual samples of the target tissues. The most common tissue sources fornon-human properties tests are the sheep and pig, but other animalsources are possible as well.

In one embodiment, once the geometry, target properties, and sourceanimal have been selected, tissue testing may commence. Using the verysimple femoral artery model brought up as an illustrative example, themodel could consist of at least two structural components (artery andsupport tissue) made from two different analog materials. If it isassumed for the sake of this discussion that the model will be used toevaluate abrasive tissue damage and ease of device passage through theartery, and further assumed that the analog materials will be designedaround porcine tissue properties, then a pig must be sourced andsacrificed to produce the required samples for testing. It is importantto note that tissues begin to degrade immediately after death sopreserved samples ideally should not be used for this purpose. The testsperformed on the tissue samples may include abrasion resistance, shearstrength, and lubricity, but other tests might be included as well.

The data collected from this testing regime will be used as a target inthe design of the analog materials, and the design intent is that theseanalog materials exhibit physical properties that mimic the physicalproperties of the target tissue samples. After the materials areformulated their performance will be verified by repeating the samephysical properties tests that were performed on the original tissuesamples on the newly formulated analog material samples. Of course,these tests must be performed under conditions as reasonably similar aspossible to the original (tissue sample) tests.

Part of the design process involves prioritizing the various targetproperties for the synthetic analog materials. Less important propertiesshould be placed further down the list and given a lower priority duringthe formulation process. This is typically, though not necessarily,required because the design becomes progressively more difficult toproduce as the number of modeled properties increases. The number oftarget properties are preferably limited to three or fewer. If morecomplex model behavior is required than this restriction will allow,then the number of components can be increased instead. For example, theartery might by constructed from three two-property analog materialsinstead of one three-property analog. Typically, a component comprisedof several analogs will exhibit a more complex (and realistic) responsethan a component constructed from a single (multi-property) analog. Inthe case of the femoral artery model, the artery component itself ispreferably composed of two or three different analog materials. Themodel may also employ multi-part components for skin, fat, muscle, andbone.

The choice of materials used in a constructing the model will to a largeextent determine how realistically the model simulates the in vivoenvironment. For example, many medical device companies presently useglass tubing to mimic portions of the cardiovascular system; however,glass is obviously more rigid than most biological tissues and tends tobe much smoother than the luminal structureal surface of diseased, oreven healthy, blood vessels. Consequently, a catheter will behave muchdifferently in a glass model than in an actual blood vessel.

The composition of individual analog materials is unimportant as long asthe relevant properties are accurately modeled. Typical engineeringmaterials, including many metals, ceramics, and plastics commonlyemployed in industry may be used depending on the required analogproperties. However, in cases where soft tissues are being modeled itwill generally be advantageous to use nonstandard materials such ashydrogels. These materials swell in the presence of moisture and canretain large amounts of water without dissolving. They are constructedof one or more hydrophilic polymer molecules, although copolymerizationwith hydrophobic monomers may also lead to the formation of a hydrogel.These materials are generally elastic, and exhibit a three-dimensionalnetwork that is either crosslinked directly by chemical bonds orindirectly through cohesive forces such as ionic or hydrogen bonding.Hydrogels are particulary advantageous in this application because theformula may be manipulated to give a combination of water content,lubricity, abrasion resistance, and other properties characteristic ofliving soft tissues. In this respect these materials are particularlysuited to modeling fragile tissues such as venous or arterial intima andciliated epithelia. Hydrogels also provide an ideal substrate formaintaining a surface of live cells if so desired.

The models of the subject invention employ a wide variety of hydrogelmaterials, including but not limited to polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, and polyhydroxyethyl methacrylate. Thisentire class of materials is physically more tissue-like simply bynature of incorporating water, but by carefully controlling suchparameters as molecular structure, density, wall thickness, durometer,and many other physical properties and characteristics a good matchbetween the actual tissue and analog material may be achieved.

Poly(vinyl alcohol) is normally produced by the acid-catalyzedhydrolysis of poly(vinyl acetate), which effectively converts thependant acetate groups to hydroxyl groups. The properties of theresulting polymer are determined by tacticity, degree of hydrolysis, andmolecular weight. Most commercial grades of PVA are stereoregular(primarily isotactic) with less than 2% of the repeat units forming inthe ‘head-to-head’ (adjacent hydroxyl groups) configuration. In theorythis should allow a high degree of crystallinity in the finishedproduct. However, this is hindered by the presence of residual acetategroups so the tendency toward crystallization depends primarily on thedegree of hydrolysis. This refers to the percentage of converted acetategroups on the main chain. Partially hydrolyzed grades (less than 75%conversion) do not crystallize significantly and are soluble in water atroom temperature. This is because the large number of bulky acetategroups increases free volume and prevents the long-range interchainassociations required for crystallization to occur. As the degree ofhydrolysis increases the loss of bulky acetate groups reduces freevolume and the chains are allowed to more closely approach one another.The compact but highly polar hydroxyl groups then come into closeproximity and ‘bind’ the chains together through strong hydrogenbonding. These interchain forces increase the degree of crystallinityand greatly reduce solubility. In fact, in spite of the highconcentration of hydroxyl groups completely hydrolyzed grades of PVAshould be heated to nearly 100 C. to attain solution. These materialsexhibit excellent mechanical properties and chemical resistance and alsoswell to a significant degree.

The properties of PVA hydrogels vary with molecular weight, but sincethese materials are normally obtained in polymer form the molecularweight cannot easily be adjusted. Instead these properties are typicallymodified by means of chemical or physical crosslinking. Chemical gelsare easily formed by the addition of agents which undergo condensationwith the hydroxyl groups on the main chain. A number of aldehydes(glutaraldehyde, formaldehyde, etc.), dicarboxylic acids (adipic acid,terephthalic acid, etc.), and metal ions (Fe³⁺, B⁵⁺, etc.) will formchemical bonds with PVA which result in crosslinks. Longer moleculessuch as diacids are generally preferred over metal ions because the ion‘bridge’ is short and restrictive, embrittling the material. Moleculessuch as adipic acid can effectively restrict chain mobility whilemaintaining some measure of flexibility.

The orientation of a given gel material may be induced by drawing thematerial, by heat treatment, or by casting the polymer in solution witha gelling agent. These agents create specific interactions between thehydroxyl groups on adjacent chains, bringing them together to improvehydrogel bonding. Many such agents are known, and this process is easilyemployed on a laboratory scale. This is the method the author employedfor the fabrication of PVA gels used in this study. The process (TableIII, see Example 1 below) is very simple and basically only involvesdissolving the polymer in a solution of water and the gelling agent,dimethyl sulfoxide (DMSO). This solution will spontaneously gel overseveral hours at room temperature or when chilled. The properties of theresulting gel depend on the molecular weight and concentration of thepolymer in solution, as well as the concentration of the gelling agent.Increasing the concentration of the agent tends to improve mechanicalstrength, but also reduces swelling. At any rate, the amount of gellingagent should be minimized because it must be extracted prior to use.

Validation of embodiments of the subject models is, in most cases, adesired objective. First, it will help determine the degree of realismof the simulation—in other words, how accurately the simulation performscompared to the in vivo environment. If the intent is to simulate bloodflow in the carotid artery, for example, one type of validation wouldreveal how flow rate in the simulation compares to the flow rate in thepatient.

Validation also identifies the limitations of the simulation. Especiallyin theoretical simulations, it is important to understand not only theaccuracy of the model but also the circumstances under which it breaksdown. A simulation might be highly accurate under normal situations, butif an abnormality is introduced, the simulated results might not berepresentative of a similar abnormality in vivo. Finally, if data fromthe simulation will be used in support of an FDA submission, it is evenmore important that the simulation be validated. The stronger thevalidation, the stronger the submission.

In general, three validation strategies are available: quantitative,qualitative, and indirect. Quantitative validation involves collectingnumerical data from the simulation and comparing it to data collected invivo under similar conditions. Collecting quantitative data usuallyinvolves the use of instrumentation—for example, pressure transducers torecord simulated blood pressure. Common diagnostic technologies such asultrasound or MRI might also be used. Of course, technologies such asultrasound are designed for use on biological tissue, and since thesimulation will probably be made of inert materials, some modificationsmay be necessary, as those skilled in the art will appreciate in view ofthe teachings herein.

In qualitative validation, experienced users (usually clinicians) usethe device in the simulation following the same protocols they wouldfollow when using the product in a patient. After the simulatedprocedure, users convey in as much detail as possible how the deviceperformed in comparison to their experience of using a comparable devicein a patient. To test a new product, the manufacturer should identifycurrent users of similar products. For obvious reasons, users having themost clinical experience will typically yield the best results. Whenused properly, the “touchy-feely” data generated in the qualitativevalidation are as important as the numerical data obtained from thequantitative validation.

Indirect validation involves the comparison of physical performance datafrom the model to the actual use environment. This is the type ofvalidation that is integral to the design process for Animal ReplacementModels. The basic logic behind this form of validation is that if theindividual model components exhibit properties similar to the targettissues then the model as a whole will exhibit performance similar tothe synthetic organ being constructed. This type of validation willtypically be followed by other tests once the model is completelyconstructed.

A strong validation strategy involves a combination of all of thesetechniques. Conducting only one type of validation leaves open thepossibility that some important piece of information has been missed.When used together, the results help maximize the accuracy and degree ofrealism of the simulation.

The model embodiments of the subject invention comprise features thatmake them valuable for medical device design and development testing.First, since the models are designed to respond to physical stimulus ina fashion similar to the target (human or animal) anatomy, deviceperformance in the model may be used to predict device performance inthe target anatomy. Second, the device interfacing portion of the modelmay be removed for quasi-histological examination, allowing the effectof the device on the target anatomy to be measured. This is particularlyimportant because it allows the potential for injury to be predicted.Third, because the device interfacing portion of the model can beremoved and replaced, a large number of tests can be performed undereither identical or varying conditions as desired. This would allow thegeneration of descriptive statistics on device performance and theexecution of meaningful designed experiments, both of which areimpossible with live animals or cadavers. Fourth, if a hydrogelsubstrate is employed to support a living tissue bed, the effect of thetest device on actual living cells can be predicted. Fifth, the modelsmay be equipped with pumps, heaters, and other accessories to moreaccurately model almost every aspect of actual use conditions. Sixth,the models may be equipped with sensors that allow the measurement ofdevice influences such as applied force and pressure on portions of thetarget anatomy. Also, these models provide a wide range of cost, safety,and logistical benefits to device developers compared to existingbenchtop models, cadavers, and live animals.

Description of the Illustrative Embodiments

FIG. 1 shows one embodiment of the subject invention directed to afemoral artery model 100. The model 100 comprises artificial supporttissue including muscle 122, skin 124, bone 126 and fat 128. Embeddedinto the artificial muscle 122 is a luminal structure 130 geometricallysimulating a femoral artery. Portions of the luminal structure walls maybe constructed of hydrogel, or preferably, as shown in FIG. 1 entireluminal structure wall is constructed of hydrogel material. Theartificial support tissue may be constructed of hydrogel material, butnot necessarily, and typically is made of other types of materials suchas latex, rubber, silicone or combinations of the foregoing. The model100 also comprises a seam 140 running along the longitudinal axis of themodel 100. The model comprises two segments 145 and 142 which arebrought together and engaged to one another by an appropriate mechanism.The segments 145 and 142 may be separated to access luminal structure130 to remove for testing and/or to replace with another luminalstructure for additional testing. For example, upon the luminalstructure 130 being subjected to a predetermined test or simulatedprocedure while in the model 100, the luminal structure 130 may beremoved to study the affect of such test or procedure on the luminalstructure 130. Once the luminal structure 130 is removed from the model100, it may be replaced by another to conduct a replicate test orprocedure, or different test or procedure, without having to replace theentire model. Those skilled in the art will appreciate that theengageable segments 145 and 142 may be engaged by one or more of severaldifferent mechanisms including, but not limited to, snap/friction fit,magnetic coupling, hook and loop, adhesives, tongue and groove, zipper,and/or latching mechanism. In a specific embodiment shown in FIG. 1, thetwo segments 145 and 142 are hinged together via a latching mechanism150 and hinges 155 such that they are separated by pivoting from eachother. This hinged and latching mechanism allows for easy and reliableopening and securing of the separate sections 145 and 142 together.Furthermore, in most cases, the testing of the luminal structure 130will involve the employment of a liquid to be directed through theluminal structure 130. Therefore, the model 100 may be equipped with apump 160 fluidly communicative with lines 162, 164 and reservoir 166.

FIG. 2 shows a close-up perspective view of a luminal structure 200 thatmay be used as the luminal structure 130 in embodiment 100 described inFIG. 1. The luminal structure 200 represents a femoral artery modelcomprising three different layers: 210 simulating the tunica intima, 220simulating the tunica media, and 230 simulating the tunica externa.

FIG. 3 a shows a perspective view of a removable luminal structureembodiment 300 that comprises branches 310. FIG. 3 b shows a perspectiveview of another luminal structure embodiment 330 not having branches.The luminal structures 300 or 330 may be used as the luminal structurein the femoral artery model shown in FIG. 1 and described above.

Further, for the various removable luminal structure embodimentsdescribed herein it is valuable that they comprise a means that allowsthe facile engagement to the model. FIG. 3 c is a perspective view of aremovable luminal structure 340 comprising at one end a magneticcoupling 342 that is engageable with a corresponding magnetic coupling344 associated with a receiving portion 346 associated with the model(not shown). Preferably, the engagement of the removable luminalstructure 340 to the receiving portion 346 is such that it liquid tight.As discussed herein, depending on the type of testing to be conducted,and the target tissue to be simulated, it is desirable to implement aliquid that is directed through the luminal structure 340. Those skilledin the art will appreciate that a magnetic coupling means is not theonly means of engaging the removable luminal structure 340. Other meansinclude, but are not limited to, snap fit, adhesive, friction fit,interference fit, or hook and loop fabric.

FIG. 4 shows a partial breakaway view of another model 400 designed fortesting medical devices intended to be directed to or implanted in aheart and approached through vasculature inferior the heart. The model400 geometrically mimics a human torso with partial limb portions. Themodel 400 comprises a luminal structure 410 extending from one of thepartial leg portions 412 to a simulated heart component 414. The luminalstructure 410 has a femoral artery region, iliac artery region,abdominal aorta region, thoracic aorta region, descending aorta region,aortic arch region and ascending aorta region. The luminal structure 410and supporting tissue region 416, i.e., tissue cooperative with andsupporting the luminal structure 410 may be made of analog materials.Typically, the luminal structure 410 will be partially or wholly made ofhydrogel. The luminal structure component 410 and heart component 414may be readily dissociable from the supporting tissue 416. As describedabove for the femoral artery model, the model 400 may be comprised oftwo or more separatable segments so that they can be separated andaccess made to the luminal structure and/or heart to replace suchcomponents. As shown in FIG. 4, access to the luminal structure and/orheart is achieved by removing a door 460 defined on the model 400. Thedoor 460 may be lifted off or pivoted open (such as by being hingedalong one edge) such that access to the internal components in theinternal chamber 470 is achieved. FIG. 5 shows a perspective view of aheart model embodiment 500 that may be implemented as the heartcomponent 414 as described above for the heart model 400 shown in FIG.4. The heart model embodiment 500 is therefore dissociable from thesupporting tissue in and around the chamber 470 of the torso embodiment400. The heart model embodiment 500 comprises luminal structuresrepresenting different coronary arteries: left coronary artery 505,circumflex artery 510, anterior interventricular artery 515, marginalartery, and right coronary artery 520. In addition, the heart embodimentcomprises an aorta 523 with branches for the brachiocephalic 525, leftcommon carotid 530, and left subclavian 535 arteries, as well as thesuperior vena cava 540. One or more of these luminal structures of theheart model embodiment 500 may be designed to be dissociable from thecontiguous supporting tissue of the heart embodiment 500.

FIG. 6 shows a transparent view of a neurovasculature model embodiment600. The model is configured to geometrically mimic a human head andpartial neck. The model 600 comprises a brain component 630 and multipleluminal structures geometrically mimicking and anatomically positionedto correlate to certain neurovasculature, such as right and left carotidarteries, 612, 614. The level of detail of the neurovasculature, as wellinclusion of certain neurovasculature will depend on the particularneeds and uses of the model 600. The model can be constructed tosimulate neurovasculature surrounding the exterior of the brain as wellas neurovasculature embedded within brain tissue. FIG. 8 is a bottomview of a brain showing, in detail, various neurovasculature associatedwith the brain. FIG. 10 is a cross-sectional view of a brain showingcertain internal neurovasculature of the brain. The model 600 may becomprised of two or more removably engageable segments that aredisengaged in order to access internal luminal structures and/or braincomponent 630, such as prior to or subsequent testing. As shown in FIG.6, the model comprises a head support tissue casing 621 comprised of aright and left hemisphere segments 622, 624 respectively, as defined byseam 625. Segments 622 and 624 may be engaged together by a mechanism asdescribed for embodiments 100 and 400.

EXAMPLE 1 Testing of a Guidewire Exchange Catheter

This following experiment describes a simple Animal Replacement Modelused in the testing of a guidewire exchange catheter. The testingdescribed includes the simulation of worst-case conditions to provide anestimate of device performance and reliability when misused in aclinical setting. This data was used to determine the suitability of thedevice for clinical trials. The materials required appear in Table IIIand the fabrication process for the tissue analog materials appears inTable IV.

TABLE III Materials and devices used in simulation example. Device orMaterial Used Quantity Device Code Balloon Guidewire 13 1 GuidewireExchange Catheter 13 2 AVE GT1 Floppy Guidewire 1 3 AVE Microstent IIStent Catheter 1 4 ACS RX Multilink Stent Catheter 1 5 Scimed NironRanger Stent Catheter 1 6 Scimed Magic Wallstent Stent Catheter 1 7Hotplate Stirrer 1 — Animal Replacement Model 1 — Dimethyl Sulfoxide A/R— Polyvinyl Alcohol (M_(w) = 130k-150k) A/R Completely hydrolysed

TABLE IV Fabrication process tabulation for poly(vinyl alcohol) hydrogeltissue analogs. PVA (99% minimum degree of hydrolysis, 100,000 minimumM_(w)) and DMSO (dimethyl sulfoxide) are used as received. Water isdistilled or purified prior to use. The resulting syrup may be castimmediately or stored indefinitely at room temperature. Step Directions1 Clean a 1.5 inch diameter glass or plastic mold (culture plate) withethanol and place on a level surface. 2 Determine the quantities ofreagent required. An 8% PVA solution will be prepared in a 1:1 mixedsolvent. 100 grams of solution will require 8 grams of PVA, 46 grams ofDMSO, and 46 grams of water. 3 Create the mixed solvent by adding equalportions of water and DMSO to a round bottom flask. Set the flask on astirring hotplate and equilibrate to 85° C. 4 Add the PVA polymer to theflask while stirring. Solution is encouraged if the polymer is addedslowly. Continue stirring until dissolution is complete. 5 Aftersolution is achieved loosely cap the flask, reduce the temperature to75° C., and continue stirring for a period of 6 hours. After this timethe solution may be stored at room temperature for later use or reheatedto 85° C. for casting. 6 Pour 7 ml of the solution into the mold andallow the casting to gel over a 24 hour period. After this time thecasting may be removed and placed in a warm water bath to extract theDMSO. Once the solvent is completely removed fabrication is complete.

Test Directions

-   -   (1) Ensure that all DMSO has been removed from the PVA disc        prior to use.    -   Extraction in clean water for at least 24 hours is required to        guarantee the purity of the disc.    -   (2) Cut a 2 inch square section off of a lint-free wipe. Wet the        center of the section with a few drops of water (don't wet the        edges), then tape the section to a flat surface one edge at a        time. Ensure that the wipe is flat before taping down the last        edge.    -   (3) Set up the Animal Replacement Model as shown in FIGS. 7A&B.        Insert a 9F guide into the glass tube so that the tip extends 2        mm beyond the end of the tube. FIGS. 7A&B show the PVA disc        secured to lab benchtop.    -   (4) Adjust the rotational position knob on the stand so that the        angle of attack is approximately 80-85 degrees. The angle of        attack is measured between the normal vector of the PVA disc        surface plane and the primary axis of the glass tube.    -   (5) Insert a 9F guide catheter through the glass tube so that        approximately 2 mm extends beyond the end of the glass tube.    -   (6) Place a PVA disc on the center of the lint-free wipe and        position the Animal Replacement Model so that the tip of the        guide catheter is centered over the disc.    -   (7) See FIG. 7B Adjust the vertical position knob on the ficture        so that the tip of the guide catheter is approximately 1-2 mm        from the surface of the disc.    -   (8) Fill a syringe (20 cc is greater capacity) with water and        attach to the Y-branch on the guide. Close the Hemostasis valve        and flood the guide so that the excess water is ejected onto the        PVA disc. The disc needs to remain completely hydrated during        the experiment, so each time a disc is replaced the guide must        be flushed again.    -   (9) Each one of the devices listed in Table III will be placed        through the guide so that it impacts the surface of the PVA        disc. No more than 8 inches of each device will be passed out of        the distal end of the guide and only one pass will be performed.    -   (10) After completion of all testing each PVA disc will be        graded subjectively following the scorecard descibed in Table V.        Blot water off of the disc prior to inspection so that the        surface may be better visualized.    -   (11) Inspect each disc and record results in Table VI. Scores        midway between those descibed in the table are permissible.

TABLE V Scoring formula for visual damage to Animal Replacement Modeldisc. Grade Comments 0 No visible damage 1 Visible mark on surface 2Compression marks or skipping grooves 3 Deep compression or grooving 4Tissue model perforation or tear

TABLE VI Individual device scores for Animal Replacement Model test.Code Score 1-1 1.0 1-2 0.5 1-3 0.0 1-4 0.5 1-5 1.0 1-6 0.0 1-7 1.0 1-80.5 1-9 1.0 1-10 0.0 1-11 0.5 1-12 0.0 1-13 0.5 2-1 1.0 2-2 1.0 2-3 2.02-4 1.5 2-5 1.5 2-6 1.5 2-7 1.0 2-8 0.5 2-9 2.0 2-10 1.0 2-11 2.5 2-121.0 2-13 1.5 3 0.5 4 2.5 5 1.0 6 1.5 7 1.0

TABLE VII Summary of device scores for Animal Replacement Model test.Code Device Mean Std Dev 1 Balloon Guidewire 0.43 0.44 2 GuidewireExchange Catheter 1.38 0.54 3 AVE GT1 Floppy Guidewire 0.5 — 4 AVEMicrostent II Stent Catheter 2.5 — 5 ACS RX Multilink Stent Catheter 1.0— 6 Scimed Niron Ranger Stent Catheter 1.5 — 7 Scimed Magic WallstentStent Catheter 1.0 —Discussion of Results

The test plan included 13 Balloon Guidewires, 13 Guidewire ExchangeCatheters, 1 standard coronary guidewire, and 4 stent catheters. Thestent catheters and coronary guidewire are available commercially in theU.S, while the Balloon Guidewire has been approved for clinical trialsin Europe. The Guidewire Exchange Catheter is the focus of thisexperiment.

The test results described in Tables VI and VII were derived from 7different devices tested under otherwise identical conditions. In eachinstance the same test fixture, with identical attack angle and tip gap,was employed. The tissue analogs (PVA discs) were fabricated in a singlebatch and were identical. All testing was performed in a single sessionby one operator. It is reasonable, therefore to attribute performancedifferences between individual device tests to the devices themselves.

The impact of each device on the tissue analog is illustrated in FIGS.9A-C. The guidewire (FIG. 9A) had minimal effect, leaving an impression(surface remained unbroken) approximately 0.15 mm in width. The AVEMicrostent II stent catheter (FIG. 9B) penetrated the surface and left amuch wider 0.70 mm groove in the tissue model. The Guidewire ExchangeCatheter (FIG. 9C) skipped along the surface of the model and createdimpressions that were as wide as 0.75 mm in some places. Referring toTable VII it may be seen that the mean damage score (n=13) for theBalloon Guidewire was less than 0.5, which corresponds to the creationof very minor, transient impressions in the model. The score range was0.0-1.0.

The mean score attributed to the Guidewire Exchange Catheter was lessthan 1.5, which corresponds to visible impressions, which may or may notresult from penetration of the surface. Closer inspection of theindividual data points reveals that the surface was actually compromised(range was 0.5-2.5) in less than a third of the specimens.

The scores attributed to the various stent catheters range between 1.0and 2.5, with a median value of 2.0. In fact, the worst damage caused bythe stent catheter group was the 2.5 score attributed to the AVEMicrostent II, which was equaled in only one instance by the GuidwireExchange Catheter in 13 repetitions.

The scores achieved by the Guidewire Exchange Catheter were lower thanthe median stent catheter value in 10 of the 13 trials. This datasupports the argument that the use of the Guidewire Exchange Catheter isno more likely to cause injury in actual clinical use than other devicescommercially available in the U.S.

Finally, while various embodiments of the present invention have beenshown and described herein, it will be obvious that such embodiments areprovided by way of example only. Numerous variations, changes andsubstitutions may be made without departing from the invention herein.Accordingly, it is intended that the invention be limited only by thespirit and scope of the appended claims. The teachings of all patentsand other references cited herein are incorporated herein by referenceto the extent they are not inconsistent with the teachings herein.

1. An artificial anatomic model configured to geometrically mimic a lumen possessing human or nonhuman animal anatomic structure, said model comprising: a luminal structure comprised of, in part, or in whole, a hydrogel, said luminal structure simulating tensile modulus and shear strength of a human or nonhuman animal vein or artery with fifty percent or more similarity, and comprising an inner luminal surface simulating a coefficient of dynamic friction of a human or nonhuman animal vein or artery tunica intima inner surface with fifty percent or more similarity; and artificial support tissue cooperative with said luminal structure and comprised of an analog material.
 2. The artificial anatomic model of claim 1, wherein said artificial support tissue is comprised of at least one analog material selected from the group consisting of hydrogel, silicone rubber, natural rubber, other thermosetting elastomers, other thermoplastic elastomers, acrylic polymers, other plastics, ceramics, cements, wood, styrofoam, metals, actual human tissues, actual animal tissues, and any combination thereof.
 3. The artificial anatomic model of claim 1, wherein said artificial support tissue is designed to simulate at least one predetermined physical characteristic of skin, muscle, bone, fat, skin, or connective tissue.
 4. The artificial anatomic model of claim 1, wherein said artery comprises a femoral artery.
 5. The artificial anatomic model of claim 4, wherein said artificial support structure comprises a material analog simulating muscle and geometrically mimicking a portion of a human thigh.
 6. The artificial anatomic model of claim 1, wherein said vasculature comprises a thoracic aorta.
 7. The artificial anatomic model of claim 1, wherein said artificial support tissue is dissociable from said luminal structure.
 8. A model designed for testing a medical device, said model comprising: an artificial anatomic structure geometrically mimicking a human or animal anatomic structure; and analog material employed by said artificial anatomic structure simulating at least one predetermined physical characteristic of a target tissue; wherein said artificial anatomical structure geometrically mimics vasculature, and further comprises: artificial support tissue; a luminal structure comprised of, in part, or in whole, a hydrogel, said luminal structure simulating tensile modulus and shear strength of a human or nonhuman animal vein or artery with fifty percent or more similarity, and comprising an inner luminal surface simulating a coefficient of dynamic friction of a human or nonhuman animal vein or artery tunica intima inner luminal surface with fifty percent or more similarity; a liquid reservoir adapted to hold a liquid; and a pump in fluid communication with said luminal structure, said pump causing a pulsed or continuous liquid circulation, said pump circulating said liquid from said reservoir through said lununal structure.
 9. The model of claim 8 wherein said luminal structure further comprises a second analog material disposed along an outer surface of said vessel, said second analog material comprised of a structural integrity simulating predetermined characteristics of an outer surface of said vasculature.
 10. The model of claim 8, wherein said luminal structure comprises a portion having an enlarged diameter simulating an aneurysm.
 11. The model of claim 8, wherein said luminal structure comprises a portion defining a restriction simulating a stenosis.
 12. The model of claim 8, wherein said luminal structure comprises a portion simulating an arteriovenous malformation or tumor.
 13. The model of claim 8, wherein said liquid comprises a color simulating an appearance of blood. 